[Insulinoma originating from transplanted pancreatic cells after low dose portal embolic islet transplantation in streptozotocin diabetic rats].
The tumorigenesis of insulinomas is unclear. Hyperglycemia has been found in many short term experiments to be one of the strongest stimuli for proliferation of the pancreatic beta-cells. After isologous islet transplantation into the livers of streptozotocin-diabetic rats it has been shown by our group that the proliferative activity of islet graft epithelial cells is strongly increased in a hyperglycemic environment (low-number islet transplantation) compared with normoglycemic conditions (high-number islet transplantation). The aim of this study was to investigate the long-term fate of these hyperproliferative islet grafts. 66 out of 91 streptozotocin-diabetic male Lewis rats persisted in a mild diabetic state after transplantation of 250-450 islets (main group), 25 animals became normoglycemic immediately after transplantation of 1000-2000 islets (control group). 5-Bromo-2'-desoxyuridine was administered prior to sacrifice. For the determination of the proliferative activity of the different cell types immunohistochemistry for insulin, glucagon and somatostatin was combined with a 5-Bromo-2'-desoxyuridine immunohistochemistry. Six animals of the main group developed insulinomas in their livers between 18 and 24 months after islet transplantation (i.e. 18% of the animals which lived more than 18 months after transplantation). The insulinomas induced severe hypoglycemia (12-36 mg/dl blood glucose), and the tumor cells showed a high proliferative activity, a positive immunoreactivity for insulin, and typical electron dense granules. The normoglycemic control group animals did not develop endocrine tumors. This study shows for the first time that insulinomas develop in transplanted islets of Langerhans under the influence of the long-term proliferative stimulus hyperglycemia.
Dombrowski
F
F
Pathologisches Institut, Universität Bonn.
Pfeifer
U
U
D000818:Animals; D002455:Cell Division; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D007340:Insulinoma / Q000209:etiology* / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000473:pathology*; D008099:Liver; D008113:Liver Neoplasms / Q000209:etiology* / Q000473:pathology; D008297:Male; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000473:pathology; D011168:Portal System; D051381:Rats; D011917:Rats, Inbred Lew; D016042:Transplantation, Heterotopic
Insulinomentstehung aus transplantierten Pankreasinseln nach niedrig doisierter portal-embolischer Inseltransplantation bei Streptozotocin-diabetischen Ratten.